Future Enrollment Research Articles

A phase I study (CA180021-Segment 2) of dasatinib in patients (pts) with advanced solid tumors

14042 Background: SPRYCEL™ is a potent, orally active, multi-targeted kinase inhibitor, active against BCR-ABL and SRC family kinases. We report the results of a Phase I dose-escalation study evaluating safety, tolerability, pharmacokinetics, and biomarkers of dasatinib in pts with advanced solid tumors. Methods: Pts with adequate hematologic, renal, cardiac and liver function received oral dasatinib once daily for 7 days per week. Three doses and schedules were examined: 90 mg BID; 140 mg QD; and 180 mg QD. Pharmacokinetics and pharmacodynamic biomarkers were collected on Days 1 and 26 of Cycle 1. Tissue biomarkers were assessed at screening. CT was performed at least every 8 weeks, and FDG-PET at weeks 4, and 8. Results: 26 pts [M=15, F=11] ECOG PS ≤ 2 with epithelial tumors (n=14) or other solid tumors (n=12) have been treated in escalating dose levels. Toxicity was generally mild; most patients came off study for progressive disease. DLTs of pleural effusions were seen in 3/9 subjects on the 180 mg cohort, 2 of whom had pre-existing effusions. Patients with pleural effusion have been excluded from future enrollment. The maximum tolerated dose has not been identified. There have been no objective responses on CT. Six patients have had stable disease with continued study treatment for 2–10 months. Conclusions: Dasatinib can be safely administered at doses of 140 and 180 mg QD. Clinical efficacy, pharmacokinetics, and correlative studies of tumor biopsy material and early FDG-PET results will be reported. No significant financial relationships to disclose.

Bayesian decision-theoretic group sequential clinical trial design based on a quadratic loss function: a frequentist evaluation

The decision to terminate a controlled clinical trial at the time of an interim analysis is perhaps best made by weighing the value of the likely additional information to be gained if further subjects are enrolled against the various costs of that further enrollment. The most commonly used statistical plans for interim analysis (eg, O'Brien-Fleming), however, are based on a frequentist approach that makes no such comparison. A two-armed Bayesian decision-theoretic clinical trial design is developed for a disease with two possible outcomes, incorporating a quadratic decision loss function and using backward induction to quantify the cost of future enrollment. Monte Carlo simulation is used to compare frequentist error rates and mean required sample sizes for these Bayesian designs with the two-tailed frequentist group-sequential designs of, O'Brien-Fleming and Pocock. When the terminal decision loss function is chosen to yield typical frequentist error rates, the mean sample sizes required by the Bayesian designs are smaller than those of the corresponding O'Brien-Fleming frequentist designs, largely due to the more frequent interim analyses typically used with the Bayesian designs and the ability of the Bayesian designs to terminate early and conclude equivalence. Adding stochastic curtailment to the frequentist designs and using the same number of interim analyses results in largely equivalent trials. An example of a Bayesian design for the data safety monitoring of a clinical trial is given. Our design assumes independence of the probabilities of success in the two trial arms. Additionally, we have chosen non-informative priors and selected loss functions to produce trials with appealing frequentist error rates, rather than choosing priors that reflect realistic prior information and loss functions that reflect true costs. Our Bayesian designs allow interpretation of the final results along either Bayesian or frequentist lines. For the Bayesian, they minimize the total cost and allow the direct calculation of the probability density function for the difference in efficacy. For the frequentist, they have well-characterized type I and II error rates and in some cases lead to a reduction in the mean sample size.

Speaking of research advance directives

To examine one model of research advance directive as a possible way to reduce the mismatch between patient and proxy choices and also to learn more about how patients with mild to moderate dementia may want to keep decision making or cede it to their proxies in the future. Separate interviews were conducted with 149 dyads of dementia patients and family proxies about future enrollment in five types of research. Subsequent joint interviews were conducted with 69 of those dyads to discuss their separately articulated decisions and ask whether the patient prefers future enrollment decisions to be made as he or she directs today or as the proxy deems best in the future. Patients chose to cede future decision making to their proxies in 82.9% of the trials. Patients ceded decisions to their proxies in 80.7% of those trials about which the dyad had given opposite answers (n = 74, 49.7%). Patients who had expressed discomfort about the prospect of the proxy making an enrollment decision in a trial (n = 49, 32.9%) ceded decision making to their proxies in 45.7% of those trials. Both patients and proxies were willing to discuss future research enrollment in the context of an advance directive for research. Such a document may be helpful to proxies and researchers in the future to judge the types of research and associated risks patients are willing to enroll in. Although most patients willingly cede future decisions to their proxies, a sizeable minority do not wish to do so.

Longitudinal analyses of four years of experience of a prepaid comprehensive medical care plan. 1958.

The spectacular contributions of science to medicine and the popularization of the results have greatly stimulated the demand on the part of the public for making modern medical benefits more readily accessible to a larger portion of the population. But the very advances which have stimulated this demand and which have focused attention on the preventive aspects of disease have also contributed greatly to the cost of medical care. On the one hand, this increased cost has led to an enormous growth in the application of the insurance principle to prepayment for medical and hospital care; on the other, it has led to new approaches in the organization of medical practice to provide this care. These changes in the methods of paying for and of providing medical care are comparative newcomers among American social institutions. Provision for prepayment of hospitalization began in 1933 with the establishment of Blue Cross plans. Prepayment of medical care is an even more recent phenomenon. Fewer than six persons per 1,000 held surgical and medical insurance in 1939. Today, according to the Health Information Foundation,2 almost 70 per cent of the population is protected or “covered” by some combination of hospital, surgical, or medical insurance. On the organizational side change has been less rapid, but there has been a steady growth in the number of group practice organizations. It has been estimated3 that while in 1932 there were 239 medical groups with 1,466 physicians in the United States, by 1951 there were 600 such groups with over 5,000 physicians. Growth in voluntary health insurance both in terms of people covered and in benefits offered will undoubtedly continue. New organizational patterns will continue to emerge. Unlike their predecessors, however, these new developments will be able to call upon a body of experience to guide them which was not available to most of the present voluntary prepayment plans for medical care at the time they were founded. The experience of one such plan—the Health Insurance Plan of Greater New York (HIP)—has been analyzed in the belief that it will be of value not only to HIP but also to administrators of other medical care plans, to welfare fund administrators, to public health officials, to community planners, to sociologists, and to the public in general, all of whom are interested in facts that bear on the problem of making the benefits of modern medical care available to the population. The HIP experience will be presented in three parts: Part I, the present paper, deals with enrollment experience and sets forth data on the extent to which enrollees of different classes remain in the Plan and factors influencing continuance of their enrollment; Part II will present information on the number and kinds of physicians’ services utilized by enrollees and how this utilization varies with length of coverage in the Plan; Part III will contain data on morbidity among enrollees of the Plan and will seek to develop measures of prevalence and incidence of various diagnoses as reflected in the operating records of HIP. These data represent the results of a “longitudinal” analysis of the first four years of operation in HIP—that is, they show the experience of the same group of individuals followed through four years of calendar time. They supplement material contained in a published report on the findings of a field survey inquiring into the health and medical care of HIP and New York City households4 which was essentially a cross-sectional study depicting the situation at a particular point in time.

State Public Policies and the Racial/Ethnic Stratification of College Access and Choice in the State of Maryland

This study uses descriptive analyses of data from multiple sources to examine changes during the 1990s in the racial/ethnic stratification of college access and choice in Maryland and to explore state public policies that may have influenced changes in the demand for and supply of higher education for students of different racial/ethnic groups during this period. We also discuss the potential implications of recent state policies on future enrollment stratification in the state.

The number of Americans without health insurance rose in 2001 and continued to rise in 2002.

Data from the Census Bureau and the Centers for Disease Control and Prevention indicate that the number of uninsured Americans rose in 2001and in the first quarter of 2002. The main reason insurance coverage fell was a drop-off in employer-sponsored insurance for workers and their dependents. This reduction was triggered by rising unemployment levels and rising health insurance premiums, which made it more difficult for employers to offer insurance or for workers to afford it. The downturn in private coverage was partially offset by increased enrollment in Medicaid and the State Children's Health Insurance Program (SCHIP). About two million mor e children and one million more adults would have been uninsured had it not been for the growth in these programs. Funding for the public programs is, however, threatened by budget shortfalls affecting most states, which administer these programs. Many states have cut their Medicaid programs and are planning further cutbacks. Increasing federal assistance to states and their Medicaid programs could help protect insurance coverage for low-income people during the current economic slowdown. Future SCHIP enrollment could drop sharply because of a shortage of federal funds, and Congress could take steps to bolster SCHIP funding.

Role of Self-Efficacy and Task-Value in Predicting College Students' Course Performance and Future Enrollment Intentions

Predictive utility of self-efficacy and task-value beliefs was compared among 168 Korean female college students. The study assessed the constructs longitudinally and attempted consolidation of self-efficacy and expectancy-value theories. Self-efficacy perceptions were assessed at varying levels of measurement specificity. Exploratory factor analyses showed that self-efficacy items were reliably differentiated into separate factors of a priori specificity. These self-efficacy factors were positively correlated among themselves and, with an exception of problem-specific self-efficacy, also with the task-value factor. A correlation coefficient between any two self-efficacy factors tended to decrease, as these factors were associated with increasingly different measurement levels. Path analysis showed that students' midterm scores and enrollment intentions at T1 were better predicted by the task-value factor. However, the typically stronger links of self-efficacy to performance and of task value to intentions were observed with T2 variables.

Who will enroll? Predicting participation in a phase II AIDS vaccine trial.

The problems of underenrollment and selective enrollment may undermine AIDS vaccine trials. If prospective study subjects' stated willingness to participate (WTP) in hypothetical vaccine trials predicts future enrollment, then measuring WTP before recruitment may enhance the enrollment in, and ethics of, such trials. We prospectively studied changes over an 18-month period in the stated WTP in, and knowledge of, a hypothetical AIDS vaccine trial among 610 Philadelphia residents at high risk for HIV infection. Of these people, 499 were subsequently recruited to participate in an actual, phase II AIDS vaccine trial. We used multivariable logistic regression and the area under the receiver-operating characteristic (ROC) curve to model predictors of actual enrollment. Actual enrollment rates were 8.3%, 6.8%, 15.8%, and 29.0% among those who had initially said they were "definitely not," "probably not," "probably," and "definitely" willing to participate, respectively (p =.006). The area under the ROC curve was 0.65, indicating a modest ability of stated WTP to differentiate those who enroll from those who do not. Knowledge of basic vaccine trial concepts, though unrelated to enrollment, increased over an 18-month period with repeated education sessions (p <.0001), whereas stated WTP declined over this same period (p <.0001). Although other factors not captured by stated WTP may also influence future enrollment, prospectively assessing stated WTP may augment the validity of the informed consent process, help prevent underenrollment, and clarify the population from which the study sample is drawn.

Who Will Enroll? Predicting Participation in a Phase II AIDS Vaccine Trial

Background: The problems of underenrollment and selective enrollment may undermine AIDS vaccine trials. If prospective study subjects' stated willingness to participate (WTP) in hypothetical vaccine trials predicts future enrollment, then measuring WTP before recruitment may enhance the enrollment in, and ethics of, such trials. Methods: We prospectively studied changes over an 18-month period in the stated WTP in, and knowledge of, a hypothetical AIDS vaccine trial among 610 Philadelphia residents at high risk for HIV infection. Of these people, 499 were subsequently recruited to participate in an actual, phase II AIDS vaccine trial. We used multivariable logistic regression and the area under the receiver-operating characteristic (ROC) curve to model predictors of actual enrollment. Results: Actual enrollment rates were 8.3%, 6.8%, 15.8%, and 29.0% among those who had initially said they were “definitely not,” “probably not,” “probably,” and “definitely” willing to participate, respectively (p = .006). The area under the ROC curve was 0.65, indicating a modest ability of stated WTP to differentiate those who enroll from those who do not. Knowledge of basic vaccine trial concepts, though unrelated to enrollment, increased over an 18-month period with repeated education sessions (p < .0001), whereas stated WTP declined over this same period (p < .0001). Conclusion: Although other factors not captured by stated WTP may also influence future enrollment, prospectively assessing stated WTP may augment the validity of the informed consent process, help prevent underenrollment, and clarify the population from which the study sample is drawn.

Managed Care and Performance Measurement

Performance measurement systems and report cards which attempt to measure and report the quality of care provided by managed health-care organizations, have become mainstream in health insurance markets as managed care penetration continues to increase. However, little is known about the impact formal plan evaluations have on the contracting and enrollment decisions made by health insurance purchasers and consumers. Information regarding the link between performance evaluations and enrollment is crucial for those charged with projecting future enrollments in and risk profiles of managed care organizations. This paper describes the performance measurement systems currently being used to evaluate managed care plans and reviews the empirical literature for evidence regarding the impact of measures on plan enrollments.

Modeled Retention and Graduation Rates: Calculating Expected Retention and Graduation Rates for Multicampus University Systems

AbstractThe State University of New York, using large databases and regression techniques, has developed several coordinated, comprehensive efforts to evaluate and project current and future enrollments.

Critical care research and pre-emptive informed consent: a practical approach used in Chris Hani Baragwanath ICU.

1) To establish a protocol within international and local ethical guidelines to obtain informed consent for critical care research, overcoming constraints previously described and 2) To evaluate eventual recruitment using this protocol. Prospective descriptive study. Multidisciplinary ICU in a community-based university teaching hospital. Following approval by the University Ethics Committee and Hospital Review Board, patients admitted between January and May 1996 were assessed on weekdays for potential enrollment into existing clinical trials. Discussion with potential candidates and/or next-of-kin occurred at the earliest opportunity and informed consent was obtained preemptively. Next-of-kin was notified if enrollment subsequently occurred. We evaluated the number of patients screened, the number of potential study candidates, the number for whom consent was obtained or refused and the number subsequently enrolled. None Of 249 patients screened, 149 (60%) did not meet the inclusion criteria. Of 100 potential study candidates (40% of all patients screened), we failed to make contact with the next-of-kin in 29 cases (12% of all patients screened). Thus 71 patients or next-of-kin were counselled (28% of all patients screened). In all, 30 patients (12% of all patients screened) were subsequently enrolled into a study. A policy of pre-emptive informed consent enabled us to overcome some of the problems previously experienced in our unit with regards to patient enrollment in critical care research. Although overall recruitment remained low, predictions for future enrollment can be made from this study.

Projecting grade-specific enrollments for school catchment areas: An evaluation of two methods

Historical enrollment data for the catchment areas of individual schools are rarely useful for projecting future enrollments because their boundaries are frequently adjusted to balance growth and decline in the enrollments of individual schools. The modifiable spatial-filter method (MSF) was developed to meet this problem (Rushton, Armstrong, and Lolonis, 1995). In this article, a modifiable catchment area method (MCA) is developed, and the performance of the two methods is compared in one school district. Both methods use individual, address-matched, student records, but are different in the way they spatially aggregate these data to estimate key model parameters. Results are clearly sensitive to these differences. We apply both methods retroactively to the address-matched student records, from 1989 through 1992, of 16 elementary schools in one school district in Iowa, and we project the 1993–1996 enrollments for 17 school catchment areas in the district. We show that the average of the results of the two methods produce projections that are more accurate than either method alone. We also show that it is the nonstationarity of model parameters that leads to different levels of performance by the two methods in certain parts of the study region. © 1998 John Wiley & Sons, Inc.

The impact of policy changes on forecasting for school districts

This paper describes a case study in which a professional demographic consulting team was brought in to aid in the development of a long-term building and reorganization plan for an Indiana school district. Just prior to the start of this process, a state-level policy was promulgated that changed the age of eligibility for entering kindergarten in such a manner that it temporarily produced the appearance of an increase in the number of kindergartners in districts throughout Indiana. For the district in question, a group of residents pointed to the apparent growth in the number of kindergartners as a reason not to close schools in their area. Having uncovered both the policy and its effect, the consultants produced an enrollment forecast that was not confounded by the artificial appearance of growth. This forecast showed much less growth than expected by the district's officials and residents, both of whom had been conditioned to expect future enrollment growth by not only the policy effect but by local media reports on the national ‘Baby Boomlet’, a phenomenon not actually occurring in their district. The demographers successfully defended their forecast in the face of strong initial disbelief as well as outright opposition by the residents. This experience tends to validate the argument made by others that the participation of professional demographers in an adversarial procedure can be beneficial in helping to formulate long-term plans.

Assessing Students' Responses toward Computer-Aided Design of Apparel

This study examined the relation of responses from two student groups toward computer-aided design (CAD) for apparel to their computer use, computer experience, or enrollment in an elective CAD course. In the non-CAD group of 46, computer anxiety was significantly correlated with computer use and computer experience as well as future enrollment in the CAD course. In the CAD group of 17, students in the CAD course were significantly less fearful of job elimination and more interested in technical aspects of computers at the end of the course than at the beginning. Data have been applied to the continued course development of computer-aided design especially for apparel-related academic programs. As one outcome, length of instruction has been recommended over a continuous 16-wk. period. Using specific instructional methods to reinforce components from both the affective and cognitive domains of learning has helped to sustain positive responses throughout similar subsequent offerings. Finally, preparation for employment was enhanced as a consequence of acquiring specific technological skills included in the CAD course.

The relationship between students' levels of school achievement, their preferences for future enrolment and their images of universities

A survey of 2000 final year students in secondary schools in Western Australia indicates that, although moderately performing students are unlikely to gain entry to university, the majority have a strong preference to attend university rather than vocational training (TAFE). Their actual institutional preferences are highly correlated with their self-perceived, level of academic achievement and their decisions on institutional preferences strongly influence their overall image of individual universities, across a number of dimensions. The research suggests that university marketing might benefit from a more thorough consideration of aspects of the marketing exercise, particularly in relation to the effectiveness of printed promotional material and whether it might more usefully target parents of prospective students.

Students first!: Reconceptualizing support services

AbstractColleges that put students first are concerned with what students learn and how they are treated. Students who are educated in such an environment receive the added benefit of exposure to quality management and customer‐oriented organizational culture. Ultimately, student satisfaction affects retention and future enrollment growth.

Perceived Risk: The Link to Plan Selection and Future Utilization

Perceived Risk: The Link to Plan Selection and Future Utilization Abstract Enrollment of Medicare beneficiaries in HMOs may reduce the costs of providing health care but has raised concerns over adverse selection and how to adjust reimbursement levels to compensate for this potential. An adjustment based on an individual's perceived health and financial risk may be more accurate than proposed demographic, prior use of health services or current health status adjusters. Results suggest that those in HMOs may be more sensitive to the extreme cost of hospitalization than those with fee-for-service insurance, and therefore were attracted to the comprehensive care offered by the HMO. In addition, HMO enrollees, face fewer barriers to seeking health care, thus may be higher utilizers in future periods. Introduction In 1985, out-of-pocket health care costs for the elderly were greater in real dollars than before the 1965 Medicare legislation[7]. This phenomenon did not go unnoticed by the elderly. Realizing they were spending more and more of their budgets on health care, they began to look for insurance mechanisms with which to supplement their Medicare coverage. At the same time, the Federal government was also experiencing changes in the health care marketplace. The Federal government has seen Medicare expenses increase from $4.7 billion in 1967 to $64.6 billion in 1984[11]. Th is rapid increase in expenditures prompted the Federal government to expand health care delivery mechanisms for Medicare enrollees beyond the traditional fee-for-service (FFS) system through legislation supporting the enrollment of Medicare beneficiaries in health maintenance organizations (HMOs). These trends at the consumer and the payor level have resulted in the increased enrollment of Medicare beneficiaries in HMOs. In 1981, 595,000 Medicare beneficiaries (a little more than 2 percent) were enrolled in capitated systems. In 1985, the number of Medicare beneficiaries enrolled in HMO/CMP and group practice prepayment organizations reached 1,117,000 or 3.7 percent of Medicare enrollees[11]. The initial contracts between the Health Care Financing Administration (HCFA) and HMOs were structured on a cost basis. This type of contract was attractive to HMOs because it limited their risk and thus encouraged them to enroll Medicare beneficiaries. In 1985, HCFA began to move away from the signing of cost contracts with HMOs to the establishment of risk contracts [13]. Under the initial risk contracts the HMOs enrolling Medicare beneficiaries were reimbursed at 94 percent of the AAPCC (Adjusted Average Per Capita Cost). This structure gave HMOs financial incentives to provide services at lower costs (one of their claimed advantages over a fee-for-service practice). At the same time, these contracts would lower the level and increase the certainty of Federal expenditures for health care. Recently, the General Accounting Office (GAO) has recommended lowering the multiplier for the AAPCC to 89 percent[15] thus shrinking the average reimbursement and creating further pressure upon providers (HMOs) to deliver medical services at a lower rate or to exit the Medicare HMO market. Problem Statement The move to risk contracts for HMOs creates a number of concerns for the HMOs operating under these terms. The primary concern is whether or not adverse selection will occur. Adverse selection occurs when the high risk/high cost members of a population tend to disproportionately enroll in one type of insurance plan[1]. Recently, HMOs have acted as if adverse selection has occurred in their Medicare population. For example, Av-Med Health Plan Inc. in Florida, Maxicare in California, and Choice Care in Cincinnati have all withdrawn from Medicare risk contracts[14]. Their actions may be in response to adverse selection by enrollees which resulted in the costs of providing services in excess of reimbursement levels. …

Reflections on Sociology Textbooks by a Teacher, Scholar, and Author

I am pleased to respond to the comments about textbooks made here by two distinguished sociology editors. Their observations raise a number of significant issues, but in this reply I will focus on areas where I disagree with one or both of them. In my view, textbooks are neither as clonelike nor as impervious to innovation as editors Fullerton and Graham suggest. At the same time, I will argue that introductory textbooks should not be the major source of innovation in a discipline. I do not see ancillaries simply as fluff that accompanies textbooks, but consider them important supplements to a text with the potential for enhancing critical thinking. Finally, the prospects for our discipline are not as dismal as Frank Graham suggests; hopeful signs for future enrollments should fortify our resolve to balance entertainment and knowledge.

Causes and consequences of student evaluation of instruction

Student evaluation of course quality was examined as an intervening variable in a path model with seven input variables and the following two output variables: (1) whether students would recommend the course to others, and (2) students' plans to take more courses in the discipline. Student evaluation of the lecturer was the most powerful input variable for the intervening variable course rating. Class format, defined as lecture or lecture with small groups, did not affect course ratingper se but did relate to students' attitudes toward taking more courses in the discipline. Lecturer and textbook evaluation had significant independent effects on whether the student would recommend the course to others. The major implication for university departments is that quality of instruction in introductory courses has impact on future enrollment plans.